Science Series 5: Larry Sherman / Understanding Alzheimer’s, MS, Parkinson’s / Music & the Brain

0:01 Welcome to another episode of Come TOGETHER. We're Live. Doctor Larry Sherman, Welcome. How are you? Great. Great to see you. Great to see you too. We are going to have so much fun I want to dive right into it. I had a whole list of your credentials, but I wanted to talk to you. The reason I reached out to you was to talk about neurodegenerative diseases. And I did see that on your, on your page. I forgot whether it was your website or university page that you that you also studied music in the brain.

0:45 And so I wanted to talk about that as well. But why don't you, you know, you just told me about two seconds off air. But tell me a little bit about the main research that you do. And we kind of break that down from there. Sure. So I went a research laboratory out at the Oregon National Primate Research Center and at Oregon Health and Science University, which is a medical school in Oregon, in Portland, OR. And I'm a professor there. And my, my lab is focused on understanding ways to repair the brain or protect the brain in people with diseases like multiple sclerosis and Alzheimer's disease or other forms of dementia. We made a, a really interesting discovery back in 2000 and, and five where we found that this molecule, you might have heard of it, hyaluronic acid.

1:33 And you watch any face cream commercial, they always say they add hyaluronic acid to it. And hyaluric acid, it's just a big old sugar molecule and people have been injecting it into joints for arthritis. Actually the number one commercial use of it was in race horses. Interestingly, after races they it's actually reduces the inflammation. But some more horse medicine. Yeah, yeah. This is not Intermectin trust. Me. Yeah, yeah, yeah. But but so it turns out, you know, when you have any kind of injury anywhere in your body, this molecule builds up as a protective response, right? It's anti-inflammatory. It kind of, you know, keeps the the tissues in in check.

2:15 The brain is really bad about getting junk out of it itself. And so this happens in the brain too. But if it keeps happening, this molecule it, it accumulates to excess. There's too much of it. And then the cells around these areas where there's damage actually make an enzyme, it's called a hyaluronic dace, which chews up the hyalic acid. And what we figured out over years is that these little pieces of hyalic acid that get chewed up feedback on the cells and tell them not to do their jobs. And so, and that's probably a protective response over time. Who knows why, but but we found out that if you block that enzymes activity that higher in a days, we can actually see repair in the brain, which is really amazing. And so for patients with Ms., it's mostly about a substance called myelin.

3:07 Myelin is, it's this kind of fatty protein substance that wraps around nerve cells like an insulation, like on a wire. But it really it's main function is to make everything go faster. I lived in Germany for 3 1/2 years, so I was referred everything relative to the Autobahn where there's no speed limit. So if you have myelin and your nerve cells, it's like driving on the Autobahn at midnight when there's no traffic and you can go 200 miles an hour and no one's going to stop you. And if you lose your myelin, it's like driving on pick your favorite freeway to drive on at rush hour, lucky to be going two hour 2 mph, right? And so you can imagine what that means for our brains because our brains have all these different parts to them.

3:49 And you have to have very high speed connections between all these different parts of the brain to make it work, right? Right. So people that Ms. their immune system is attacking their own myelin and stripping it off of these cells. And so now these different areas are. Attacking their their brains. Yeah, they're attacking their brains. Yeah. So, so, so that's so the result is now these areas, it's like you've got all these areas that are supposed to be moving on the Audubon, and all of a sudden it's like you're they're not moving at all, or they're moving at 2 miles an hour. And so now movement is affected, feelings are affected, being able to see all these things are affected and even even learning a memory can be affected. Yeah. So what we found out is that if we block this higher on a dace activity, we can actually get some of the myelin to come back. And maybe it's not getting you out of the Autobahn, but maybe it's getting you up to legal speed limits in the state of Florida, so.

4:41 I see, OK, there's I have a lot of follow up questions, but that was that was that was an awesome introduction to this. To be clear at the beginning, right, you said so the way that the problem begins is by our body's immune system, our natural immune system, whose job it is to attack potentially dangerous cells. Every time that it functions, some of it makes its way to the brain. Is that what you said? So, yeah, our immune system and people that mess, OK, what's happening is your immune system is, it's supposed to be attacking foreign things, right? Like bacteria, infections or viral infections, right?

5:25 And in this case, for some reason that we still, we're not entirely sure about a people with MS. what's happened is their immune system has decided that their myelin, which is this really important substance in the brain, is a foreign body. It's not supposed to be there. I see. And so it's getting into this, immune cells are getting into the brain and attacking the person's own myelin that's and someone. Someone whose brain is but but but everyone's brain has myelin in it because anyone whose whose immune system is working means that they have to have a mile a certain amount of myelin in the brain, period. Right. And if your immune system is working right, it's not attacking your myelin, right? That's one of these. It's an autoimmune disease. It's your immune system attacking you as opposed to attacking things that shouldn't be there.

6:07 Crazy, crazy. So it's interesting. It doesn't sound, you know, the way that I've heard, for example, diseases like dementia or Parkinson's is like the connection between the our brain is faltering, is my understanding, the connections kind of dissolving. This isn't so much that the connection dissolving as much as they're slowing down communication almost to a halt, right? Right. So that's a different thing and but there is a longer term consequence of that. So it turns out one of the other things that myelin does is it keeps those neurons, the nerve cells healthy. So over time, what happens in Ms. patients is I see the neurons start to die. And so now you do start to lose all these connections, and that's a real problem. So that's where the neurodegeneration comes in. Exactly.

6:52 The brain is attacking the protective part of the neurons or the body. Yeah. The wow, Yeah, wow. Now it, now in Alzheimer's, what's happening is, and, and you mentioned Parkinson's. I mean, Parkinson's is really interesting because it's really selective neurons that are dying mostly it's so-called dopaminergic neurons, which are, you know, important for ulcer movement, coordination and everything else, among a lot of other things that we don't talk about with Parkinson's patients, but that they also experience. And in Alzheimer's though, it's, it's even broader. It's, it's more lots of different nerve cell centers where the nerves are really dying off. And now my own research on on Alzheimer's about the hyrinic acid is we, we see the changes in myelin happening in Alzheimer's patients too.

7:35 So this protects the substance, but now it's, it's just damage to the neurons and myelin is going away because of the damage associated associated with the neurons, but it's not coming back after the damage the way it does and other diseases. But in addition, what we figured out was that hyrinic acid actually helps protect blood vessels in the brain. And, and what's amazing we think is that the reason it's doing that is, is it's responding to some sort of long term inflammation, all the other things that we do to our bodies, long term hypertension, all these things. And eventually again, the cells want to clear that stuff out with these higher endidases. And So what we're finding is that this higher endidase activity may lead to leaky blood vessels in the brain, basically because the cells are dying in the tiny little blood vessels. And so we may have a second benefit of blocking this activity by protecting the brain's. Blood vessels, I'm sorry.

8:34 And leaking blood vessels in your brain could lead to strokes or God forbid, or blood. What's the consequences of that? So, so, yeah, in a big sense, for the bigger vessels, yeah, that's a stroke. For these tiny little vessels, though, they're more like a little tiny, tiny mini strokes that you probably don't even notice. But over time, as those pile up, and now you add to that the things that happened in Alzheimer's, which are these things called plaques in these two angles, and you put all that together, that's when you really have a problem. That's because it's not just the plaques and tangles, it's not just the vasculature, It's that combination that seems to be read. Hey everyone real quick if you're enjoying the show, click subscribe and rate the show. 5 stars helps a ton. Thanks so much.

9:20 Really driving dementia so. Wow, wow, wow. OK, that's crazy. That's all, that's all. And and I guess this process can begin. Is it this process happened quickly? Does it happen over the course of time? Because I know, for example, actually, and is a pretty crazy story. I know someone from college who I think when we were 25 married a 35 year old girl. And I think within a couple, I, I think within a couple of years she was diagnosed with MSI. Thought that. And, and my previous association with Ms. was that it manifests in people's sixties, 70s. You know, I didn't realize that it happened that early. Yeah, I mean, people in their 20s and there's even, you know, there's pediatric forms as well.

10:05 But wow, really? And this is a disease that, sadly, even today, you don't really know you've had it until you've had it for a while. I met the actress Terry Garr years and years ago who had Ms. And she was telling me how, you know, she was hanging out at a party one time, and she woke up the next morning and she had a real weakness in her arm and was about to go to the doctor. And then it got better. So she didn't go. And then a few years later, it happened again. And this time it lasted a longer. She still didn't go to her doctor. And then finally, like 10 years later, she had this attack where she's really not feeling well. She finally went to the doctor and they finally got diagnosed.

10:48 So by the time she was diagnosed, she'd already had this disease for a decade. And she was in her 30s, you know, her late 30s and, and and she was trying to hide it from people, too, because in Hollywood, you know, people with disability not to get jobs. Yeah. But but yeah, she said, she's really had a lot of disability long before she even got diagnosed. Wow, wow, wow, that's OK. That's crazy. And I guess it gets worse over time. And at a certain point you can't, you can't fight it, right. And the only, the only reason why I think why, why the story strikes so is because on one hand, it feels like every time that anything happens, you know, I mean, I'm 30 and like, my back is just starting to, you know, hurt me more often. Or, you know, I'm getting more.

11:36 Taking a little longer to recover. I'm at the age where when I wake up and I feel all the pains in my body thinking I'm still alive because I know the pains there. But, you know, you never know whether to take, you know, what to take seriously or not. You know, and like, I guarantee you that I've woken up with, you know, pins and needles or something weird happening. Like, I don't know, that's weird. I just kind of get up and I forget about it and like years between episodes would even imagine is like you can't even connect them necessarily. No, no, absolutely not. That's actually, that's absolutely right. And and that's the thing. So the cool thing about Ms. now, compared to when I started this research, we used to have like one or two drugs and I've got over 20. Yeah. And these drugs are great because what they're doing is they're stopping your immune system from getting into your brain, right? So they, they really slow down the progression of the disease. So people are living longer and better than MSL than they have ever before, but we still haven't addressed the ability to repair that damage that happened leading up to where they are now.

12:36 And so that's what my lab is trying to figure out, and that for both Ms. and Alzheimer's. Why has that been so challenging? So, you know, the brain is kind of is, we still don't know as much about the brain as we do about other organs. And that's because the brain is this amazing computer and there are so many, you know, think about the billions of cells and trillions of connections between cells and that brain and all the ways, different ways that it works. And you know, it's funny because I talk to my students and they're like, you know, what's the most surprising thing to you right now about research? And I said, well, when I was where you are, we didn't know anything that we know right now. And it was All Star Trek.

13:19 It was all like, you know, this is, this is like science fiction. And now it's like, Oh my gosh, we can actually, we may actually be able to cure some of these neurological diseases, you know, which is incredible. We have proof of concept that that's true from various experiments and model systems, right? So, so that, but that's been a challenge because there's so many things we still don't quite understand to the point where we're going to have an effective therapy. I'm actually giving a talk, a public talk about the history of Alzheimer's disease. And I talked with and it starts in ancient Sumatra from these old tablets they found describing elderly people who have these symptoms that are very unusual. And it's it's Alzheimer's disease. And then we had nineteen O 6 when Alzheimer himself made these initial observations about what was happening. And so we took all that information, did all this modeling looked good, and then we took it to the patients and lo and behold, it didn't work.

14:15 And the reason is we there were things we just fundamentally didn't know yet. And we made assumptions based on what we knew and, and what all that told us is that we need to know more. And that's how science works. So we're getting better. We're getting better, but we're not there yet. We are, we are. I mean, and you know, I've talked about this a bunch and everyone in the world is pretty much talking about it. But you know, the, the, our ability to be able to access information nowadays is going to is so dramatically different overnight. You know, I mean, I, I'll, I'll tell you that, you know, the part of the way that might go by my podcast, for example, is I use AI to help me find guests, right? But I want to talk to, you know, 10 people about the brain and music or the brain, you know, the history and you know, economics, whatever.

15:00 And please find accessible people that you know, have given public talks and have the emails available online, right? That, that process in of itself to find 10 people to reach out to two years ago, what took me hours and hours and hours a week, and now I am reliably finding, you know, top quality, really great guests in a matter of minutes and just the amount of efficiency of wedding out information sorting through data is just so incredible. I'm, I, I feel like we definitely I, I, you know, my, my opinion with a lot of technology today is that we're so far past where we've been cabled. We're able to implement at the moment and like all of this is like waiting for us to just like decide as a world to like pick it up and start using it, but like it's all just sitting there in front of us.

15:50 Well, in my field, I'm just in my career time, you know, it's been incredibles watching how things have progressed. I mean, you mentioned information processor, just finding people or finding information. So when I was in Graduate School, I had to go to the library and we had these monthly books that were like this thick and the paper was onion skin thin. And the text was like 8 point text, right? And you had to go through and like look up subject, your area of subject and like find the papers that were recently published in your subject. And then you went to the library and you made photocopies of the articles and you brought them home and you highlighted them with a pen. Now you just type it into the computer. It likes gives you the list and it actually downloads the papers for you. And then it highlights the areas that are interesting. So it's, it's completely different. And then the technology for what we do in my lab, you know, like things that when I was in school that would take me a week to do, I can do in 30 minutes now.

16:41 So we're now we're kind of where the compute in the biotechnology, we're kind of now in that spot where it's exponentially growing, kind of where the computer, it's kind of where computer industry was 20 years ago. So we're like at the point where it's like discoveries that used to take years, now we're taking months. And soon it's going to be weeks and then it's going to be days. It's, it's remarkable. It's an incredibly exciting time So long as like our funding and infrastructure actually stays in place where I think we're going to be able to make some amazing discoveries. Yeah, and I think it's part of the reason why it's being slow rolled. It's because our friendly infrastructure needs to keep up with it. I mean, whether you're in, you know, South Florida, like where I am now, or even in when I was living in Seattle 5-6 years ago, you know, I mean, I, you know, Seattle was not prepared. The infrastructure was not prepared for the amount of people that were living there.

17:28 And I know this from driving around and local parking and, you know, these two way streets that have absolutely no business being two way streets there. And, you know, and, and like, on one hand, you know, it's, it definitely adds the charm. It's fun that the city is packed. It's fun that people are always on foot. But you can see that the, you know, we, it could have used some slow rolling before Microsoft and Boeing and Starbucks and everyone, you know, and everyone just popped up overnight, not overnight, but seemingly overnight. And, and yeah, that's really amazing. So now that we understand a little bit about Parkinson's and Alzheimer's and Ms., first of all, is Ms. or all these diseases rather, are they purely genetic or can they be caused by environmental factors? That's a really good question.

18:13 So it depends. They're all different. And the answer for that is different for each of those diseases and for any neurological disease or any disease in general. So genetics plays a part at so many different levels, right? So there's just the sequence of your genes, right? The little four letter code, and some people have subtle changes in that for a little letter code that makes genes more or less efficient in what they do. And so for Ms. for example, there's some data now suggesting that people with MS. have a genetic liability to get Ms. And by liability, I mean they have a subtle change in some genes in their immune system in particular probably maybe some subtle changes in genes and the cells in their nervous system that if something else happens, they're going to get Ms. whereas if other people had that something else happened, it wouldn't make a difference. So more.

19:09 Trigger happy? What's that? So more trigger happy. More trigger happy. Yeah. So, OK, so the trigger actually then for people who have that genetic liability, there's been a lot of different suggestions of what that might be. But one of the leading suggestions right now is a virus called Epstein Barr Virus. Now why do I know? Why do I know that name? I'll tell ya. So for, for one thing, Epstein Barr virus, 100% of humans at some point in their life where we're going to get infected with Epstein Barr virus, right? For the vast majority of us, it's a cold. For a small number of us, it's mono mononucleosis, the kissing. Disease, right?

19:50 So, so and so why do some people get mononucleosis and some people get a cold? Well, it's again, genetics probably. It may be just the state of your immune system at the time that you got infected. It may be the age you got infected. All these things together may impact that. Now for it turns out for an even smaller number of us, there are certain cancers that are related to Epstein Barr virus infection and Ms. So, so if you have that specific genetic liability and it may be more than one gene, it may be multiple genes. That are altered and then you get this Epstein Barr virus infection at some specific point in your life that means you're being triggered to get Ms. So that's Ms. right.

20:35 That's a very kind. And the reason Ms. is not I mean about a million people in the US get Ms. but that's not a really common disease. But it's it's pretty common. But it's it's still you have to have these multiple things happen to get it. So it's not as common as other things. In the case of Alzheimer's, there's a small proportion of people with Alzheimer's who have an actual mutation in a gene or, or or a different couple couple of genes. And those people tend to have this very aggressive early onset form of Alzheimer's. So that's that's different than the Alzheimer's that people get starting in their 70s and 80s or 60s even is that. What Robin Williams had, because I know that he, he got a fairly young age, I think, right, I mean.

21:19 So Robin Williams actually had a, what we think we think was a combination of Parkinson's and something called Lewy body disease, is my understanding. That's that's a little different again. And Lewy body disease is something that often goes hand in hand with Parkinson's, interestingly, and we don't entirely understand why, but for these Alzheimer's patients, yeah. So there's a small percentage of them get early onset Alzheimer's and that seems to be a genetic disease almost purely that's genetic, although there's other factors there too. For the majority of us though, as I mentioned, it's a combination of having maybe hypertension your whole life and or diabetes and then having a little bit of genes that are predisposing you towards this. Now you put all that together and you get someone who's got what we call dementia, and that could be Alzheimer's or other kinds of dementia.

22:11 So, so that's a combination of lifestyle things or things that have happened to you, plus some genetic liability. And then for Parkinson's, again, there's actually a couple of cases of Parkinson's that are linked to a specific gene mutation. Those are rare. Those are rare, but there's some data to that. Things that happened to you and things that you're exposed to can trigger that. There's a study that suggests that if you've had multiple concussions and plus you're exposed to a certain pesticides that were common, for example, in the 60s and 70s, my my brother had Parkinson's disease and the body disease and he was an athlete.

22:52 So he got lots of concussions. And that was back in the days where it's like you got hit in the head and your coach said, I got your bell rung, go back out there. So nobody recovered from the concussion back then and he was having his face rubbed in in these chemicals that were in the grass to keep the grass and the weeds away. Oh man. Right. That combination is is suspected to really contribute to Parkinson's and people who don't have the genetic Parkinson's form. So there's a lot of different reasons you can get Parkinson's, it turns out. Are there any studies about, I guess, athletes having a higher rate of Parkinson's because of that? There are some studies that suggest that that especially people, like I said, have had multiple concussions and that's also true for certain dementias. So I mean, you think about it makes sense. You're, you're causing a lot of stress to the cells in your brain.

23:41 And so as you get older, the normal stresses of aging now we're going to be amplified a whole bunch, right, right. So. Right, right. And what about what people call preventive maintenance? You know, in other words, what can we do to keep our cells healthy? Now, I know the way that you describe that Parkinson's and Ms. in particular seem to work is that it's almost beyond our control as far as, you know, what we do, right? These are things that are happening on a, on a molecular level or cellular level that, that, that we can't really control as far as we know. What is? Is there anything to do to to lower your chances of this or to slow the progression of it or what? What?

24:24 How does that work? So probably not to stop the disease from happening in the 1st place, but there are things that seem to really help with regards to progression, like you say, like making sure it doesn't get worse or, or, or progresses very slowly, but also maybe starts much later in life. And so there's this whole idea that of reserve, you know, if you have more cells to kill off, it'll take longer than for it to affect you personally. And so that's, and that's where my interest in kind of music comes in actually. So, you know, so I think there is this kind of, there's a study that was done brilliant idea. It's like the question was, how do we get a population of human beings together where we can rule out as many variables as possible to understand normal aging, right, as well as abnormal aging.

25:14 And so somebody had a brilliant idea to use nuns. So this is called the nun study. And the idea was they found a convent where they had a huge number of sisters. One of the cool things about this convent was they all had to write essays about why they wanted to be a nun to get into the convent. So this was when they were in their 19, you know, late teens, early 20s, most of them. And you can learn a lot about a person from a writing sample. And so they had that and then they followed these sisters until they died. And what came out of the study was there were there were sisters in this convent who lived to be in their 90s and hundreds and were sharpest tacks. And then there were sisters who even at, you know, in their 40s and early 50s started showing signs of decline mentally. And there were a couple of things that sorted out who got what.

26:07 One of them was the writing sample. So the sisters who were kind of more flourished in their writing, kind of more descriptive, more expressive. They tended to do better than the sisters who just said, I want to be a nun, you know, because the nuns are cool, you know, or something like that. I'm, I'm obviously oversimplifying dramatically there, but that's part of the idea. The other thing though that really was interesting was the nuns who did well were actually throughout their lives constantly trying to enrich themselves. They were trying to do like learning to play the piano at age 70 and then going off and giving piano lessons. The nuns that weren't doing well, they were kind of couch potato nuns, right? They were coming into this convent and they were taking on some menial task and sticking without their whole lives.

26:53 And so the ones that were challenging themselves, you can see that they had different brain structure. So although they had all that plaque and tangle and everything else, the rest of it was pretty well. So the plaques and tangles made less of a difference for them as they aged than the ones who just weren't developing and keeping their brain healthy. And so I think that really says a lot. I mean, the brains kind of A use it or lose it organ and everything. Well, everything is but yeah. But I mean, the brain, you got to keep doing things. Otherwise it's just going to, you're going to have less to lose as you get older. And I think that is really telling. So when I started working my music stuff, I it's amazing. Musicians have all these cool things in their brain, like more myelin, for example, evidence that they're actually maybe making new neurons throughout life because they're really intense. They're practicing their instruments or learning new instruments.

27:44 Neurogenesis, right? Neurogenesis, I learned recently. That's right. Yeah. So it may be driving neurogenesis, myelination and more synapses, more connections between neurons. And so that's the other thing that you lose in in dementia is the connections. And you know, these trains of connections, as they start to fall apart, your personality falls apart too. So if you can have more of those going into a situation where a disease is causing that loss, you have more to lose and more time. Yeah, and so, so interesting. So cool. So, so freaking cool. This makes you know this also makes you think of and I thought the portrayal was incredible. I showed this to all my high school students inside out and inside Out too did such a great job, especially in the second one of introducing the notion that as our as our brains develop and become more complicated and our emotional states vary with it, you know, and there's direct relationship between our, you know, the development and progression of our brain.

28:39 But then it would also stand to reason. And I told my, you know, I say this every time I talk about this, I would watch 100 movies of inside out, just of different phases of different people's lives, you know, just to just to watch that same, you know, concept in action in different applications. But one of them has to, you know, in and I talked actually to, I'm forgetting his name, Bob Levinson out of Berkeley. He's and yeah, he's, he was, he was super wonderful, super informative and fun and sweet. And one thing that we were talking about was the personality, I guess, loss of emotions as you age, because I was talking about my grandfather and how recently he's had short term memory loss, probably borderline dementia, but you know, they're not going to talk about it in that sense.

29:25 And I've noticed that his, you know, his range of ability to express different emotions has been significantly limited. And I'm sure no coincidence, you know, we aged 5, you know, five years every year after you retired, you know, every time, you know, he was a doctor, he was a gastroenterologist that was a very active Miami Beach. And then, you know, the second that he stopped seeing patients and the second he stopped running around and making house calls and keeping up with people, you know, the decline, the decline began almost immediately. Well, that and that makes total sense, right? If you think about it, I mean, our brains are who we are, right? Our memories are who we are. So all the things that we've experienced throughout our lives shape our personalities.

30:06 They shape everything they are that we are about us. And as those start to fade away, other aspects of our personality change as a result of that. And, and that becomes, you know, really hard over time, especially for family members who are trying to connect with these people who suddenly aren't who they used to be. And those social interactions are incredibly important. You mentioned your, your, your grandfather was constantly in touch with people. And, and when we lose those social interactions, that actually is another way that our, you know, keeping our brain active when we, we're talking to people that's gone. Those, those, those stimuli go away and, and it becomes harder and harder over time to kind of replace that.

30:48 I think there's been a number of studies done comparing people in the US to people and for example, different parts of Asia where families tend to stick together more, right? So even though you may retire from your work, you still have these intense social connections with your community and people in your family, and they tend to do better as a result of that. I think there's good data for that now. So I think that's such an important aspect of it. And then with music, you know, the same thing. Music brings you together. Music's amazing too, because as we age, one of the things, the last things that goes is music. It turns out, even though there are people who cannot speak and yet they can still sing songs that they know from their past and musicians who can sit down at at their instrument and play their instrument perfectly even though they can barely say a word. So that's amazing to me too.

31:35 I have personal experience seeing this. I've never seen anything like this before. So a girl I dated, her mother had a variation. It was a very, very murky diagnosis of Parkinson's because it didn't really match up exactly. But it was the closest that I think the doctor, the doctor's able to provide. And but a lot of the she didn't get as much of the tremors as much as she would freeze up and lock up and music. And you turn on music and you turn on James Taylor or you turn on, you know, some old show tune that, you know, hello, Dolly, That we, you know, that that she used to listen to her, she plays the accordion and like, and you would see minute to minute someone that could not move, could not like, you know, just stuck where she was to literally skipping around the house. I mean, and I saw his known eyes. I couldn't.

32:25 And I and I and I, and I mean, we definitely do not have not I guess scratched the surface as to what music is capable of impacting us, but it's, it's, I'm, I'm very hopeful for the future of that. Well, and music therapy is now being recognized more and more as a viable and actual thing that some insurance companies are actually starting to cover. My favorite, my favorite example was Congresswoman Gabrielle Giffords, Mark Kelly's wife. OK, so she, you know, she went to a campaign to that years ago in Arizona and got shot in the head. I have some crazy person. And so she wound up doing this incredible multi year rehabilitation and she couldn't speak for for a long time after being shot. And so one of the things they're having her do was music therapy where she was she she she couldn't speak, but she could hum and sing a little bit.

33:20 And over time she kept pushing herself and pushing herself to use music and she could sing phrases instead of saying them. And then after doing that for a long time, they're really pushing herself with the music. You may have heard her speak. She's she's giving talks in front of audience. Look it up. I'll look it up again. What's her name? Gabrielle Giffords, she's a congresswoman from Arizona and Mark Kelly or her husband, who is the astronaut and and he's a senator now, you know, cared for her. And it's an amazing story, you know, but, but so one of the. So that to me tells me that, yeah, music therapy is real. You see it with Parkinson's patients. Actually.

34:00 You mentioned movement. There's a lot of therapies where they're getting partners at Parkinson's patients to work with them to do dance lessons to music. The music has a rhythm to it, and the rhythm actually helps them coordinate their movement and it makes them feel less agitated and more in control, which just dramatically improves the quality of their lives. And then for Alzheimer's patients, yeah, I mean, you can sit them down in front of these, you know, can sing music from them, from their past. I have a great story about that, actually. So years ago, I was asked to do a a interview on a radio show. And the other guest was a woman named Naomi Lavelette. And she is a classically trained pianist and has now gone off and made records. And she writes music now.

34:45 And, And somebody, a family friend of hers had a dad who he was a pianist and he used to make up all these songs. He had a huge number of songs that he wrote, but he never wrote them down and he never recorded them. And all of a sudden he was at the piano and he's was forgetting whole phrases of music that he had composed. And it turns out he had early onset Alzheimer's. And so she would sit with him at the piano and find the music, the project, saving his music. And she wrote it down and she recorded it. And then I got to meet him years ago before he was really debilitated.

35:29 And we started talking about how music is like threads. We had, he had this description of music is like threads that bring people together in all sorts of different ways. It's these strands that bring people together. And I thought that was really beautiful. And about a couple months ago, I don't know if you know, Dolly Parton has basically made arrangements of her music for symphonies. No, I did not. It's awesome. And so we went to the, we went to the Symphony and it's a great show. And she, you know, so the Symphony Orchestra is playing her music and they've got some musicians and vocalists singing and it's it's an amazing show. I mean, even if you don't like Dolly Parton's music, it's amazing.

36:10 And then there's videos of her talking about the inspiration for the songs in between. And you learn a lot about her and and her life. She talks about threads, how music is like threads that bring people together. And I turned to my wife that night and I said, that's what Steve told me. This, this composer. And the very next morning, I get a call from Naomi saying, hey, Steve's on his deathbed. He's he's at end stage. Would you want to come down and see him? And I said, of course, yeah. Because I got to know the family over the years, and she came into his room and would start playing music. And here's a guy who's literally immobile on his bed. She's playing the music on her guitar and he's tapping away. He's just moving away.

36:55 And so that just tells you that. And I'm sure it helped him with his agitation and made him feel better. And you know it, It's so powerful. And I think the fact that more and more people are starting to recognize this is, is good because music is so important to humanity. It's it's, it's important to who we are as human beings. Yeah, yeah, I, I've been advocating for, I mean, probably over a year now on the show for people to go to as much as many live music events as possible. Even if even if you don't play, you know, even if you don't know it, you know, find a local bar, find a pub, find a brewery. If you go to there, there there is something that is particularly cool about a relative.

37:36 Like I would say, like the problem is I don't even know if it's amount of people relative. It's people to space, right? So, I mean, if you're in a in a little jazz club and there's 50 people there, that's awesome. I've, I've been to Blues bars in Chicago with my dad and yeah. And it's 2:00 in the morning and we walk out after hearing this band play, you know, for three hours and, and we walk out and we just feel like different human beings. And we're like, we just had this incredible shared experience and we, and also the, and with there's this unspoken bond between the people that experience that together. When you, when you find out that someone else is a deadhead and you find out someone else like Fish or Springsteen or Billy Strings or, or any, or, you know, or Bill or Billy Joel or Fleetwood Mac or anything that you like. And like, all of a sudden there's a kind of sense of camaraderie that goes like there's something that that that's unspoken and deep that you guys both share and relate to that is really, really powerful. Well, that and that's an important point. So in our book, you know, we, we, we actually send out surveys to people, a lot of professional musicians, but also just a lot of people who like music, asking them about experiences. What do you think their brains doing when they're composing, when they're performing, when they're practicing, when they're listening?

38:45 And in the listening section, so many people talked about times when they were just depressed or something was happening in their lives and then going out and hearing and experiencing a live music. And that or it's sometimes even though they're just listening on the radio and how the music kind of brought them back and helped them get out of it's deep depression or addiction even. And and it was, it was just amazing hearing these stories. But that comes back to why, Why do we even have music? Why is music so important to humans? And there's all this data now that like performing music in particular together in a groups has this amazing neurochemistry behind it. That doesn't happen when you're just by yourself. So if you think about a chorus singing together, one of the things that happens when you're singing with a group is there's two neurochemicals get turned on dopamine, which is a reward signal, and endorphins. Endorphins are really cool because they actually make you not care about pain.

39:41 But when you put that dopamine and that endorphin together, it actually gives you a sense of acceptance within a community. So you think about humans, we, we need to live in groups, we need to live in communities. And what music does is it brings us together and it makes us given that sense of belonging. Like you said, if I, if I like the dead, which I do and I find out the dead, we have a lot to talk about and we're like in this community, right? But I think think about going to synagogue and chanting. I was going to. I was literally about to bring that up. It's such a fundamental part of religious life too. It is for sure, And churches and everything else you know, I mean music. Is the best music.

40:21 It's it's all the great. Things you together. Town and everything Blues came from, I mean, it's some of the best music in the world came from churches. But it but it brings people together who have similar beliefs and similar, you know. Values. Yeah, looks out of the life and, and, and values and, and it gives you that sense of community and humans need to have that. We're we're not good at going solo. And and so I think, I think that's an important part of the evolution of music. It it it actually helped us evolve as a species and survive because it it enforced that sense of community and belonging. Yeah, I have AI. Do I have a very strong sense of optimism and hope actually for this, for this upcoming generation, because I think that they saw the pain. You know, I was born in 95.

41:06 I grew up just about the time like I I would grew up the the year that I was going through puberty and dealing with fear of girls and everything like that was the exact time I got a phone. I was able to start texting a girl instead of talking to her face, you know, and oh, man, yeah, exactly, you know, and then. And that's, that's a whole different conversation, man. It's a whole other world, but but I think that the generation below me saw the damage that it did and I and they're rejecting that. And I think that, you know, it's been coming. It's becoming popular to go to the movie theaters again, to go to live shows again. It's popular to put your phones down or to take social media fast or breaks that people take. Because I think that there's a recognition like, listen, I, I I've been saying this for 10 years with this is a test Bunny generation of social media, right? So, you know, we're like, we're letting it go. We're going to let everyone use it and we're going to just figure out whether it's good or bad and good luck with the rest of it, you know?

41:58 And I think that that that that people are picking up real quickly that this is not something that is attainable and that we do need these relationships and connections and embodied experiences for sure. Absolutely. And, and that the phone's just not going to replace that. And the way that it tries to replace it I think is incredibly damaging. And so I, I think it's, you're absolutely right. You're absolutely. Right. I wonder if there's a relationship between you between especially like scrolling and the type of the type of phone use that people use and the and and the brain degeneration. Do you know if there's any research on that? So there's growing, there's some growing studies about it. And I mean, there is some really interesting data that just came out about AI use. So people who are using AI to do the work that they used to do with their own brains.

42:45 I, I think there's some, some real evidence that you're, you're, you're actually giving up neurons for that or giving up circuits at least, right? Because, because these people are showing signs that it's not helping them in terms of normal brain processing. And it makes sense, right? You're, you're basically giving up what your brain should be doing to something else. And it's, it's becoming making your brain that couch potato brain again. Exactly, exactly right. So, so I think, I think we were going to be like you said, I think there's a test buddy generation for social media and now we're the test buddy generation for AI and we'll see how that how far that goes.

43:26 That we learned from social media, from AI, because they're making a lot of very similar promises. You know, I mean, Mark Zuckerberg running around saying that you're not going to need to hang out with friends ever again. And Sam Altman running around saying that, you know, you never have to work ever again. Like no one says that that's the yardstick that we're going for. I don't know who decided that, you know that that's what the way we're supposed to measure success or failure. Yeah. So if you're never and, and and bigger questions too, like if you're never going to work again, well, how are you going to make money? How's the average? Average, I'm not as worried about money as I am about meaning. I think, I think that we're at a point with a combination of energy and compute and robotics that I mean, especially at the rate that they grow like you and I were talking about earlier, like such an exponential rate. I I don't think capital is going to be as much of a problem in the future as much as meaning and purpose. It depends.

44:16 I think if you if you're an ultimate capitalist, you know the goal, the goal is to get as rich as possible, but that that capitalism always has winners and losers. Mm hmm. So and then I. Think we'll be post, I think we'll be we will impose capitalism pretty soon is why that you're already kind of there. I think we I have to because, because you know, I just think about in the old days, you know, if there is some new technology that came along that basically meant a whole bunch of people suddenly became unemployed. My favorite story about that, by the way, is telephone operators #1 Employment Opportunity for women in the United States. Telephone operators and and the cool story about that is kind of funny story is that there was some town where there was a telephone operator and her husband owned a Brickyard.

45:00 I think it was a Brickyard. And whenever she got the calls for another Brickyard, she would send it over to her husband's business, right. And the other Brickyard found out about that turned out to be a very guy who was turned out to be very inventive and an inventor and figured out how to do the automatic switching and went overnight. Overnight, all of those women lost their jobs, you know, all across the country. And So what did they do? So they found other positions because things were changing and there were other jobs and there was other ways to get employed. But I think the end result of AI is there will be no jobs, right? And so for some people, that's great. But for an awful lot of people, what are they going to do? And how are we going to, how are we going to feed them, you know?

45:42 So, yeah, So I do wonder about that. And I think that I'm coming back to the brain, you know, I think, yeah, again, if you're, if you're just instead of thinking about something and like you said, working with other people to come up with ideas and working at a group and now you're just plugging it into AI and all of your interactions now are over the computer instead of other people. I think that's incredibly unhealthy for our brains and and for our ability to stay happy and and everything else in our lives and fulfilled. One of the things that I found amazing. I know you've been if you've been following the whole Artemis 2 journey. The astronaut Coke was her name is her name.

46:23 She's she's she's incredible. I heard something her talking about when they were going up and coming further and further away from the Earth and just realizing that the four of them in this tiny little space were a crew that depended on each other to survive, right? I mean, everything they did, everything had to work exactly right. And they all completely relied on each other. And, and, and then she's looking at the Earth and she's seeing this Earth surrounded by blackness and realizing that the Earth is a, is a lifeboat, right? It's, it's and, and, and then she says, you know, I look back and then she says that's the crew. Everybody on that planet is a crew. And if we don't work together, we're not going to survive.

47:05 And I think that's absolutely true. Even on the one to one basis, our brains want that social interaction. They need it. And we need to be able to work together. And, and maybe that means more, we just need more choirs so we can all sing together. But I always joke. I always joke. Wouldn't it be great if we get Congress to sing? But can you? Imagine. Yeah. Or Aaron Rodgers. He says he wants anyone in public office to take ayahuasca first or something like that, you know? But yeah. And that's Yeah. And you know, what do you, what do you think? Are you aware of the Apple TV show Plebeis? Yeah. I I watched it, I love it. What do you think of that context? What do you think of concept I mean? I mean, it's, it's crazy, right?

47:49 Because it's like, I mean, it takes the work life balance question to a whole new level, right? That's severance. Oh, I'm sorry, That's severance, Yeah. Where? We have the group, the group. Things except for. The people who, Yeah, yeah, except for the people who really want to stay individuals for reasons that they don't understand. I can't wait for Season 2 to come out. But yeah, I mean, so again, coming back to social things, I mean, that's that's kind of the extreme version of that, right? Yeah, I think that's that's that's. Utopia. I think a variation is utopia. I don't know if it is because again, I think we also find a lot of fulfillment in our own individuality. Yeah.

48:34 All right. Yeah, it's, it's almost, it's almost like the the the extreme version of communism, right. So you, when you lose that, I mean, that also gives you a loss of control over things that gives you a loss of I mean, obviously if you're in that particular situation that you don't care about that anymore because you've been programmed not to care about that. But the reality is as human beings, that's not how we are. We we want to have an. Autonomy. We want to, we want to know that we're part of something. We want to know that we're part of that and that makes our brains happy. But we also want to know that we are also individuals and that we have that sense of who we are as people. And so I think those are both very important things to hold on to. Sure, sure. I watched a really interesting debate that I started showing my high school students this week with Tucker Carlson this week.

49:22 And there was ACEO of some gene editing company. And the company allows you in a similar way to IVF, the way that you can kind of select a, you know, particular traits, you can select traits like height or you could, you could actually remove, you know, I guess remove the take a embryo that is not going that doesn't have the genetic tendency towards, you know, schizophrenia or cancer or dementia or Alzheimer's. Is a lot of this research going to be obsolete if all this is just kind of edited out, or are we going to still have to experience this? We're a long ways away from it.

50:04 First of all, like I said, there are things that happen during the course of our lives that impact these diseases, right? So even if you have a genetic resistance to something or or not a genetic liability, there's still a chance you're going to get it. But more importantly, you know, the thing with gene editing is there's a, you know, there's, there's a response to everything you do. And a system is complicated. As a human body, you take out, you take out an alter 1 gene. How does that affect everything downstream of that gene or around that gene, right? So we don't really fully know. So I mean, on the one hand, gene editing. Alter the gene. The argument was to select a gene that wasn't that embryo, that was not dis, that was not just what sorry, that was not that didn't carry it. So it's not to take it, even change it, but it's to say you have a selection of 10 embryos and you know this embryo is going to be XY and Z and this one's going to be XY and Z, but to the real specifics.

50:59 We, we kind of do that already in IVF. You know, we look for embryos that are more viable, more, you know, healthy, working viable. So the, the biggest problem and the biggest challenge for IVF is, you know, it takes a lot of tries, a lot of embryos before you get one that's healthy and right. So we're already doing that to a degree, and we are at the point where we can sample a single cell from an embryo and not disrupt the embryo and do all that genetic screening already. And so it's expensive, but you can do it. So and if you're spending 30 or $40,000 a shot to do IVF, you want to have the embryo that's going to be the one that's going to be OK.

51:39 So that makes total sense. So I think we're kind of already doing it. We can do it more in a more sophisticated way, obviously, and really get down to the nitty gritty. And of course, you know, there's always ethical concerns about, you know, wanting to make all of our embryos blonde haired, blue eyed babies. And so that's another question that we as a society need to grapple with. But correcting disease genes or selecting against those? Now some people will tell you and believe and understandably that IVF is generating life, right? So every single one of those embryos is a potential life or potential human being.

52:21 Somebody can say it. And some might say those blastocysts, which are just a small collection of cells, they don't have anything yet. Just it's just a pile of cells is still a human being, Right. Yeah. So ethically speaking, is it hard to, like, pick one and let the others go? It's a hard. Question that's also interesting, right. And do you think it's not really a justification to say that those that those wouldn't have made it anyway and that every time they could only you can only procreate? You know, I guess you always right. That doesn't sound like a good enough moral justification to me. If that's if that's your beliefs, there are. People, there are people in my life who have various genetic diseases and I, I love them and they've made amazing contributions to the lives of the people around them. And it's like, would you take that away? So those are huge ethical questions that we need to grapple with.

53:09 Or, or someone I, you know, I and you know, the person that I, I dated, you know, one of the questions that, that, that was a conversation that my parents had to sit me down for is like, listen, if you want to, you know, marry this person, move on with this, with this, with this, with this girl, then you have to consider the family genetic tendencies and like whether it's her or whether it's going to be your kids, God forbid, or, or anything like that, Like this is something to think about. And you know, it's not pleasant. It's really, really not pleasant. It you know, it takes a fun la de da reality and and and makes it very real very quickly. Well, the, and so one of the other areas of research in my day job is a, is a group of conditions that are kind of collectively known as neurofibromatosis.

53:51 It's actually 3 or 4 different diseases or five even. And these patients develop horrible multiple peripheral nerve tumors and they have all sorts of other problems as well and. Different nerve tumors called pain, right? Some do, some do. Yeah. And in fact, one of the one of the forms of this disease, the main problem that these people have is, is pain, like intractable pain that there's no treatment for, which is one of the things my lab is working on actually. How do you tackle that? Well, so it's a very different kind of pain than any other kind of pain you've ever seen. And so we've we've been studying the mutations that are linked to this disease and realizing that those mutations directly cause the cells to cause nearby nerve cells to be hyper responsive to pain signals.

54:38 And so, so right now we're trying to. You know, without, is there inflammation there? Is some there is some inflammation, but you don't need to have inflammation to have this pain sensitivity. That's the thing that was. So surprising. That's crazy. And so your body wouldn't notice and relief because there's no inflammation. Right. So the question is how do you turn that off? And so we've we've identified some proteins that we think are driving this and it turns out there was already drugs available attacking those proteins for completely reasons. And so we're trying, we're trying those drugs. A colleague of mine is running a clinical trial to try to see if that will relieve the pain in these patients. But what's you know, so but these are people who know they have a genetic disorder, but also want to have families. Yeah.

55:21 So for for them, it's, you know, how do I screen for that? And for them, it's no question. I don't want an embryo that has these mutations. I want the embryo that doesn't have those mutations. And so I. Don't know if this is AI, don't know if this is a thing outside of the I grew up in. I am Orthodox Jewish. I grew up in the Orthodox Jewish world and when I was in high school we went through. I went through. I grew up in a Conservative synagogue, so. There you go, beautiful. And and I did something called J screen. I don't know if you've heard of it. Yeah, yeah, yeah, yeah. Is that, is that something that everyone does? Because I did it in high school and everyone was like, listen, you should do this because it's important to know that whoever you you know, you you should know your genetic tendencies before you date and get married so that you have an idea as to like whether you should even begin a relationship or not even, you know, I mean, I know a story of someone that, you know, got a miss the doctor misdiagnosed.

56:12 They both were carriers for Tay Sachs and, you know, and their first kid ended up dying. Unfortunately, you know, it's just terrible story. You know you want to. You want to prevent that. You know, I, I, I remember having that conversation with my parents. It's like, you know, as a Jewish family, you know, we have to worry about Tay Sachs disease. And I'm like, what Tay Sachs disease? And now of course I know what it is, but I don't know anybody who was going out before they dated and doing the genetic screen. I imagine that is in our future, to be honest. I'm sure certain people are like, I'm not going to even date you unless I know you're, you've got a pretty clean genetic background. Sure. And The thing is it's a risk, but it doesn't necessarily mean anything's going to happen, right. So that's that's the other thing, you know, if it's usually these rotations are on one copy of your gene, not both copies. So your chances of passing out on your children are small, are smaller.

57:06 But yeah, it's it's it's an interesting question. And again, that's one of those things that's like, where are we going with this? And now, you know, even the, the 23andMe and these other companies that do genetic testing for you, they have that information. Sure, Yeah, yeah. And so there's like databases. It's like, okay, you know, I'm going to, Efron's going to go date my daughter. Let's look at the genetic information up before you have that first date. Because if things go get hot and heavy, I don't want anything. Out of that, I've done that. So my, my, my, my brother is in the ultra orthodox world. And there's a, there's another program they called Dorya Sharim. And it's, I don't even remember what.

57:47 I don't even know what it means. It's translated to something about straight generations or healthy generations and didn't even tell you whether you're prone or not. What you do is you and your and the girl you're dating send in your, the, your, your report to someone. They tell you whether or not you're a match, yes or no. Like they don't tell you your whole list of potential. Do they just say there's nothing to worry about, you're good to go. And so that way you don't necessarily know your genetic history. You don't have to, but you know that you're, that you and your what and your partner are not going to be carriers for the same things, which I think is also an interesting method. But that happens before you go, you know, probably after the second or third date. If you, if you want to continue going out with my son, my daughter, we got to find out, you know what the story is over here.

58:29 That's really. Interesting. Yeah, so tell me. So let's talk about your night job now, because it sounds like you're, you know, your day job keeps it keeps you pretty busy. And you, you know, you, we discussed some of the music, but why don't you elaborate a little bit on what, on what you, what you've been doing? So this all started because I was playing piano at A at a party for our department. It was like our 20th anniversary or something. And this person comes up to me and, and, and says, I didn't know you played piano. I go, yeah, I've been in bands my whole life. And we started talking. It turns out she is the person who gathers people from the public together every year and they have these these talks and and she said, well, would you want to do one of these on music and the brain?

59:12 So that sounds like fun. And she goes well, and I'd like you to play piano somehow during the talk as well. Could you do that? I goes, sure, that sounds like fun. So I spent like 6 months reading all the papers so I could get my hands on about music and the brain. And what really struck me was the fact that some of these studies were completely relevant to what I was doing in my lab. So the idea that practicing music may actually drive more myelin formation, the idea that practicing music may actually Dr. Neurogenesis and the formation of new sets, synapses. And so I, you know, sadly, you know, that was one of these fields where about 1/3 of the papers were just crap. I mean, they were just like, you know, sample sizes of two, no controls, all these things.

59:52 And so it's like, OK, I threw that out and then I took the best papers and I kind of piloted how it related to my work. Found some good jokes to tell. I I Did you ever see the 2000 year old man with Mel Brooks and Carl Reiner? I did not. Look it up. It's hysterical. So basically Mel Brooks, famous actor and and director and writer, plays the 2000 year old man. And Carl Reiner plays the interviewer and he's like asking him questions where things came from. And so at one point, Carl Reiner says, well, where did music come from? And Mel Brooks's character says, oh, music. It came out of fear. He goes, fear, what are you talking about?

1:00:32 He goes, yeah, one day I was out walking and a lion started eating my foot off. So I called out, a lion is eating my foot off. Somebody call a cop, right? And then people heard that and came from all around and they liked it so much they started singing along. And that's how music started, right? So I put that in there and I put some music in. I get people to sing the end of Hey Jude in three different keys just to show how the brain just transposes music without any musical practice or experience. And it's, it's fun, right? And so I gave the talk and people come up to me after the talk and say, how much do you charge for this talk? And I said charge. And so because I thought this was going to be a one off as a favorite of my friends.

1:01:18 And so that turned into probably I've probably given this talk 600 times in six different countries. And what's that been every it's been a kind of fun adventure. My my wife thinks we should do it on cruise ships. You know, I think you should do. Then she gets to go, then she gets to on cruises, right? So, but it's been amazing and I've learned so much about connecting with the public, about science communication. And so that turned into other talks on other subjects. I did one about the neuroscience of love, love and pleasure, which is great because you can talk about, you know, why eating a piece of chocolate that makes your brain light up when you fall in love, all the different stages in love. And how about the neurochemistry changes when you're first meeting somebody, then you get infatuated with them and then you decide, or am I committed or am I going to start all over again and all the changes that happened there. But I also get to talk about things like when pleasure goes wrong, like depression, this is could be talked about and addiction.

1:02:16 So I mean, it was a, it was really a powerful thing to do. And then I've done a bunch of other subjects too, but the music in the brain one is always the most popular. And then somebody I know in the publishing world said you should write a book about this. And my first response was, there are so many books about music and the brain. This is Your Brain on Music by Dan Levitan is. An amazing brand. I heard there was this record. The second one was also very good. He's great, you know, and I'm, I'm. Trying to get him on his secretary pushed me off a little bit, but I'm gonna, I'm gonna, I'm gonna get him at some point. Keep working on it because he's actually really great to interview. I've heard to him a couple times and I've seen he he was here live in Portland. I got to hear him talk not too long ago, but so then then I the funny story. I play racquetball at the J, the Jewish Community Center, and it's at 6:00 in the morning because we both have jobs by my Rocket Ball partner and I.

1:03:12 And it was 1 morning after I'd given one of these talks here in Portland. And he said, hey, how'd your talk go? And I started telling him about it. And there was this guy kind of in our locker room that was kind of there. I said hi to him. I didn't know who he was, but I just said hi to him and he said hi to me. And he stops us. He says, did you say you were given a talk about music in the brain? I said, yeah, he goes, I've seen your talk twice. I just didn't recognize you without any clothes on, right. So, so, so then, so then we start talking and it turns out he's a music professor and a professional jazz musician and all these and we became friends over the years. And to the annoyance of my racquetball partners, we had these long conversations like, come on, we got to get going.

1:03:53 And then he he told me after about 5 or 6 years that he was about to retire. And this was just a year or so before COVID. And I said, you know, I got this idea. I said, you know, listen, Dennis, Dennis, his name's Dennis Plies. I said I would you be interested in writing a book with me about the neuroscience of music, where I could talk about the neuroscience and you could talk about pedagogy, learning and everything and what it's like. To be a musician. And put it together. And then maybe we could, like, send out a survey to professional musicians and add to that and put this whole conversation together and all these different things. And he said yes. And so it was moving at the speed of evolution because we're both busy people. And then COVID it.

1:04:37 Suddenly we had all this time to write. So I thank COVID for letting me finish this book. And it was published by Columbia University Press, which was awesome. They've been great. The audio version just came out. We just had the Mandarin version come out in China, in China. And they changed the cover. It's funny that it looks like something from the 1950s beatnik movement, but that's cool. I like that. It's been an amazing adventure. So I got to like just recently got invited to do my talk with the Detroit Symphony in Detroit, which was amazing. And you went and I've done. What's that? You're going or you went. I already did it. I did it back. To you nice, nice, nice, amazing and by. The way Detroit, it's really nice now. I loved it. I I.

1:05:17 Was there. I was there two or three years, two years ago when my buddies got married there. I had a great time. I had a great. Time that's a great city so we had a we had a really good time and it was really fun working with the Symphony there and and these jazz musicians there too. I asked these, I asked musicians to join me on stage, but I do this and I always ask them to do crazy things and they always buy into it and it's so much fun and we have a great time. But so that's how that all got started. And so to me, it's been an amazing adventure because I, like I said, I I'm finding things that I do in my lab life that overlap with the science behind the music, even though I'm not personally doing the science, I'm reviewing it for other people and then transmitting it. And for me, that's just been a great adventure. Yeah, one thing I was talking to Karen Barrett about who I just recorded with three or 4 episodes ago, was that she was saying how her research followed her curiosity and trail of interest rather than having an end goal in mind and just trying, you know, with tunnel vision to get there. And, and we're talking about how some of the most fun and fulfilling and creative work and some of the most, you know, progressive work, you know, that really, really pushes the boundaries come from come from this place. And, and you know, and then, you know, and people I love how you describe as like a day job and a night job, but they all flow into one another.

1:06:34 And, you know, and ultimately, you know, again, I ended up reaching out to you because of your night, you know, because of your night job. And you work on music too. So you know, the fact that the fact that people I, I, I, you know, people feel like they have a job that they're married to and that, you know, they don't have time for themselves. And I think that we need to, you know, we're having, I'm sure we're having, but we, you know, what we can really use. And you know, this would be the glass half full perspective of AI, you know, doing a lot of work. Is that for a lot of people of the question of what would you be able to do? Because all of a sudden very real. And the question is, isn't what, what, what you know, whether or not you could do it. The question is, do you have the courage to be able to do it?

1:07:16 Or are you going to be able to chase this? Or, you know, is this, are you, are you comfortable? Is this inconvenient? You know, like, do you feel, you know, I don't really feel like getting up in front of a bunch of people or I don't really feel like taking that chance at open mic and, and playing all woody and clunky and, you know, feeling embarrassed in front of everyone And like, so I'm not going to do that. But I but, you know, I think that there's going to be so much potential for, there's going to be, I hope, an exploration, an explosion of just humanity as is really, really what I'm hoping for. Yeah, because I mean, I'm the kind of person who loves to be just really busy all the time. And, and one of the nice things about being these two different lives that I've got right now, it's I'm learning. Both of those are informing each other. I'm a much better public speaker now because I decided to take a chance and do something a little wacky. And I'm, and so that also translates into how I give talks at scientific conferences, for example, on my, on the science I do in my lab.

1:08:08 And then vice versa, that my interests in my lab are driving. Well, what's, how's that? How's music affecting that? And then I can dig through the literature and find things where that that over wraps. But having said that, I, not everybody is insane as I am. And so having like you said, these tools like AI, I, I think it's going to be helpful for you. It could be freeing. It could be freeing. It could be freeing totally. I'll tell. You the only thing I've used the AI for lately is this public talk I give on the history of Alzheimer's work. So I used one of the one of the platforms to make some images. And how was that? How do you find that? My so my idea was to have a road called the amyloid plaque road, right?

1:08:50 OK. And then have a turn off and have the car miss it and they take a left and then take this left turn. And I and I asked it to just have the car hit a brick wall. So it drew this really bizarre brick wall right in the middle of the road, nothing else around it. Right. I was, I, I was about to like tell it to do it again and like make it like a, a parking space where it actually, but no, I thought, this is weird enough. I just relieve it because the whole point is we went down that path of research and which felt right for so long that we didn't feel like we needed to take that turn off. And then we hit the brick wall and that's exactly what it did. And so then I had and then I had the car go back and find that turn off again.

1:09:30 And then I added a road said said blood vessel changes and diabetes and all these other things. And then they converged to the cure, right. So that to me, that was an incredibly effective way for me because if I had to draw, that would have taken me hours. Sure. And and it's it was an incredible time saving tool. It's the only thing. No, it's because I love it. And I call the talk the long and winding Rd. So that's also my. Lovely beetle. Also another good one. So sure, sure, sure. Coming from coming together, absolutely I get. That, yeah, but. I think I yeah, the other thing I'm really passionate about is education and alternative forms of education, because I think that I think that we're at a point where we could really kind of customize and personalize an enormous amount of education based on someone's preferences. And I know for myself, I, you know, I was always, I always loved the sound of the piano, but. And I started playing guitar at 25. I'm 30 now.

1:10:28 So I started, I started taking lessons at 25, about three years and two or three years. And, but I always loved the piano, you know, and, and, and I sat down the other day and my brother has a keyboard and I was visiting home for Passover and I asked Chad GBT for just basic scale practices and finger exercises to just get comfort on the piano. And I felt this incredible rush, like almost like a weight falling off my shoulders while I'm playing. And I felt like, I was like, I, I, I, I, I felt tangibly moved just from practicing and playing. And I, I only, I put a timer on for 10 minutes because that's all, you know, I thought was, OK, I'm going to have to get myself to, like, do this. An hour went by and, you know, it felt like a blink. Oh, yeah.

1:11:14 What? What is that? Yeah. Well, and so that's another thing that I love about these, these studies on on the effects of music and also personal stories that people have come up to me with after I've given these talks. Sure. Is that you're, you're doing something very focused that involves fine and gross motor movements. It involves sensory, you know, feeling things because think about what your brain is doing when you're practicing an instrument. All right, so let's say you're reading music. All right, so let's say you've got music coming off of an iPad or a phone or, or a page. So those photons have to go into your eyes, go to the back of your eyes where your retina is. That's where all the cells that you know, take in the light go.

1:11:55 That information has to go to the very back of your brain recognized as stuff. And then the rest of your brain like figures out what it all means. And then it transmits that information to parts of your brain that plan what you're going to do with your hands. And then that plan is put into a program of motion and that's sent down your spinal cord all the way to the ends of your fingertips. And then you finally hit the the note or notes with your hands. And then your hands are transmitting information back up to your brain all the time up to your spinal cord, back up to your brain to say, OK, he did it or he did it wrong, right. And then you're, and then there's this part of your brain that's emotionally responding to what hearing your, your ears are processing information to let you hear what you've just played and your brains processing it.

1:12:36 And then you may also have an emotional response like, I love this song or I hate this song, right? All these things are happening in picoseconds, right? And so, so when you're doing that, what you're doing is you're challenging your brain in ways that just other activities don't do as nearly as much. And I think it's incredibly stimulating. And it actually, you know, I've talked to so many people who great story. I, I, I was giving one of my talks that afterwards this woman and her husband came up to me and, and said, Hey, this is the second time we've seen your talk. We saw the first time was about six years ago. And I said, that's, that's thanks for coming back. She says, well, we want to tell you about what your first talk did for us because turns out she had been a professional violinist and she got in a car accident and suddenly her motion was incredibly restricted. And her doctor told her, you know, give up the piano. I mean, give up the violin, It's, it's over. And she got incredibly depressed, right? And then they came and saw me talk about plasticity and how the brain, you know, just practicing drives all these changes.

1:13:42 So her husband says, listen, OK, maybe you're not going to play the Brahms Violin Concerto anymore, but maybe you could play bluegrass, right? So she picked up her violin. And her husband shared with me. It was painful because I had to listen to that sounding like a cat being tortured to death. But she pushed herself to play it again. And now she's in a blue. And now she's in a bluegrass band and she's and she's incredibly happy, right? It changed her life. And I think that's the power that musical practice and musical accomplishment has. When you get to the point where it's so motivating to try something and get to the point where you succeed and then you go to the next thing and you succeed again. And then you build on that and build on that.

1:14:24 And you know, I think that's an incredibly powerful thing for our brains. And it's actually physically changing our brains and and benefiting them. Coming back to that question to preserve right when you do these things and challenge your brain on your life, not only can it make you feel better, but it actually gives your brain more resilience over time. Yeah, yeah. Tell me about some of the bands that you played in. It's some of the music you play. So the first. I'm more into that. I'm interested in that too. So the the first band I played in was called Star Jammer. Nice. Wait, and where'd you grow up? You grow up in OR in Oregon. No, I grew up in La Jolla, CA mostly. I actually I was born in the Bay Area. We moved to upstate New York.

1:15:04 We were in Westchester County for a while. My my dad worked for IBM so he was an Armoc. And I was in Rockland. I grew up in Rockland. There you go, there you go. And then he got an opportunity to move out to LA. And then in LA we finally moved to San Diego when I was, you know, about 7 or 8 years old. And so mostly San Diego. So I my mornings were spent surfing. Nice. I played some baseball. I did everything you can do in San Diego in the sun all the time, riding my bike around. But yeah, my first real band was Star Jammer and we all had long feathered hair and everything else. And, and then I was in a new age, a new way, not a new age new wave band called The Pedestrians.

1:15:47 That was actually really fun. When I was in college, I used to play. So it was rock, rock, new wave, that kind of stuff. You know, this is back in the days when Quadrophenia first came out. So we loved The Who and we loved that kind of music as well. When I was in college, I hooked up with a bunch of people who like to play Blues. So we, we, I suppose, doing a lot of Blues and a little bit of jazz. And then actually, it's funny, when I was in Germany, I lived in Germany for 3 1/2 years for my postdoctoral training. And we we formed a band and it was me on on keyboards, a, a, a Dutch guy on saxophone, an English guy on on bass, and then a Austrian guy on guitar. So not one of us were Germans.

1:16:36 Nice. So we called ourselves foreigner in Germany. Wow that's that's a cool sound though. The piano, guitar, sax and and bass. It was awesome. And we did a lot of covers, of course, and we made a lot of really funny songs about the institute at parties and everything else. And that was, you know, that was really fun. And then over the years I've done these and now I play the piano and this, this talks I give. So I, I and I play everything from classical to jazz to, to pop stuff and get people singing and everything else. So it's been all It's a lot of fun. There's something about the piano, you know? I'm a Springsteen nut. I'm a Dylan nut. I'm a Grateful Dead nut. I'm a Van Morrison nut. You and I have very similar playlists. Yeah, I bet we do.

1:17:20 I bet we do. And and the my favorite songs that these that these folk have written in for example, Thunder Rd. or like a Rolling Stone. These are written on the piano and then converted over to guitar. Why do you think I feel like the piano is a better instrument for songwriting than a guitar might be? Yeah. And I think, and that's because think about what you're doing when you're playing a piano. It's it's probably, it's pretty challenging, right? Because you've got these hands that are opposites of each other. Our thumbs are both on the same side, right? And our keys are on the opposite sides. And so, you know, usually when you're playing piano, especially with modern music, you're kind of replicating a bass line with your left hand and you're playing the melody with your right hand.

1:18:10 And so it's really easy to kind of put those together for a song that you're going to now put onto a band or or even an orchestra, right? You can say here's the bass, here's the rhythm, here's the melody or whatever it is. Yeah, I mean, Beethoven often composed at the piano, right, even when he was going deaf, because he knew that he could get this kind of one set of sounds on his left side and the other sets of sounds on the right side. So. So it's it's it's a great instrument for composing because you've got both of that happening. You know, with a guitar, you're limited to the one line, right? The bass line or the OR or melody stricken, the chords are struck taking away.

1:18:51 But that's hard to do on on a on a on a both both this things sing together that kind of instrument or you get a violin or anything else. So. So you think it's just a matter so, so it's a matter of access and a matter of having your entire, I guess the structure of a song laid out in front of you with the piano that makes it that makes it easier to to navigate. Right. And of course, you can sing at the same time, right? So you could be playing bass line chords or accompanying the melody and then singing the melody. And so that makes it a really easy to compose at the piano. If I mean George Gershwin, another great example, right? He often composed at the piano and then his brother Ira would try to find lyrics that match the music, which was always kind of funny when you read their dummy lyrics that they would put in and then they put it all together. But but that was for that was orchestral music, right? That was stuff that was meant to be for a large number of instruments that would be added later once they kind of figured it all out on something like a piano. Cool, awesome.

1:19:47 And the last question and then I'll thank you for your time. There's been so much fun. Can you tell me a little bit a couple of fun facts about the, the neuroscience of love for, for I think that I think it's a really cool and interesting topic. And maybe maybe some fun facts that we could talk about in a couple of minutes. So, you know, if you think about love, there's three major phases. There's the the first, the meeting phase where you kind of see somebody across a room and your eyes lock. And that's situation, right? No, that comes next. So, so it's so the first meeting phase is where you just see someone and, and there is this, this thing that happens, your eyes lock on that person.

1:20:29 And it involves circuitry in a part of our brain that's right here. They're called the orbital frontal cortex. And what's happening is if you actually, if it's going to work, couple things have to be happening. 1, you have to both look at each other and stare under their eye, other eyes even from across the room. And then if both of you happen to be kind of in the same phase hormonally? Interesting, I think you both happen to be smiling if you're both like in a social mindset or whatever like that. Well, not just that. Like for women? You know. Physical hormonal stages, right so where are you in your cycle? There are start parts of the cycle where you're going to be more attracted to one kind of person, but maybe you'll be attracted to somebody else visually attracted if you're in a different part of your cycle. And it turns out men, it turns out men also have fluctuations in their hormones that will like drive preferences for people with like more feminine versus more masculine features, which is really interesting.

1:21:25 So all that has to be all right. And so then you have so that's, so that's the first phase, right? Just kind of meet and getting like, oh, this is, this is this person's interesting. I want to go out with them. So then you've had a few dates and now you're at that infatuation phase that you mentioned. And that is involving a whole different set of neurotransmitters. And it's almost like a disease because you're thinking about this person all the time, to the point where you're talking about them to your friends and your friends just wish you had shut up already about this person, almost. School, whatever it is. And it's also becoming almost intrusive because you're like at work trying to get work done. It's like, I wonder what she's doing right now, you know, and she's probably the, she's probably the same way, hopefully.

1:22:09 And there's other issues that happen when they're not In Sync that way that change the neurochemistry of that. So if that all works out and you go through that infatuation phase and all these things are happening and it's actually interesting. It's interesting. The next phase is commitment. So there's all this really interesting data suggesting that certain genes make people more likely to become committed in relationships. And if you don't have those genes or if you have a change in those genes, you're really, it's really hard for you to get committed and you wind up going back on that roller coaster all over again. And so this was actually demonstrated really fascinating work in these little rodents called Prairie bowls. So rodents are not generally monogamous. They, they fool around a lot, right? That's why there's so many of them. And so there's these animals called they're voles. They're these very cute animals.

1:23:03 And there's one type of Ole, not all voles, one type of Ole called the Prairie vole. And it turns out that they kind of bond for life and the males even help rear the the offspring. And they found out there's this one particular gene in in these voles that seems to dictate that behavior. And then they looked at men who were in relationships that were like steady relationships versus men that just could never make a commitment. And it turns out they had that mutation in that gene that for people while they were calling it the divorce gene. And which is not accurate, but there's more to that. But but it's remarkable. So it's like it really brings back questions about how our genes dictate our behavior and our personalities more than we probably think they do.

1:23:50 So some of me. Genetically genetically disposed to non to being committed or not committed Non committal non committal rather. Yeah, that's kind of amazing and kind of disturbing. So, so, so then it's like, you know, once you get to that committed phase, there's all these other genes that come into place that, you know, I've been with my wife for 30 years now or over 30 years. And, and I just feel really at ease when we're together and, you know, Despite that, but there are some people who never get there, right? They never had that sense of ease with the person that they're with. And so that's, that's turns out our genes kind of dictate that to a degree. So, so it's just a fascinating area and and you know, when you think about pleasure and how that relates to love, I mean, it's a lot of the same thing.

1:24:37 It's like this feeling of reward, dopamine comes back into the picture again, reward system when you're, when you feel like you're with this person and it's like just a rewarding experience. So it's a lot of the same chemistry. And I always related to like compare that to eating a piece of chocolate, right? You get to a point where you've had too much chocolate. It doesn't mean you stop liking chocolate. You just need to stop eating the chocolate for a little while. And then later on you can have some more chocolate until you get sick. So, but yeah, it's, it's, it's it, it's an amazing area of research. And I love, I love getting, of course, I always give that talk on Valentine's Day because that's, you know. Of course, of course. That's super cool.

1:25:17 Wow, so much fun, so much time to think about. Also, there's so many different layers. And you talk to 100 people and I'll tell you not even 100 people, but you know, I mean, there's also the psychological aspect of it of kind of like the familiarity versus not. And then they're growing into, you know, a different sense of relationship. And then there's the I've heard that smell has a lot to do with attraction. And enormous. Amount. Yeah. So that's. So that's the other thing. And that's. And that's partly hormonally driven, interestingly. So depend on where you are in the cycle, certain smells are going to be more attractive than others. And taste. And it turns out it tastes too. When you kiss somebody, turns out, you know, kissing is not something humans have done all along. It's it's something they figured out later. But when you kiss somebody, you're you're sampling the taste of their saliva and there's molecules in the saliva that actually may dictate you came back to the question of compatibility, right? Like, yeah, to make sure you don't have taste socks. So it turns out that you're actually tasting immune competence.

1:26:13 Wow. And and so recognize. That right, Yeah, unless we, unless we or like subconsciously do. You do subconsciously because it's a bitter taste when you're not compatible. Wow, so. So, so it's, it's really remarkable. And then there's this really funny thing that was going on for a while several years ago where that's coming back to smell, right? They would actually have people spend their day like sweating into these shirts. And then you would take your shirt off and put it into a bag with just a number on it. And then somebody would come and smell the shirt. And if they had that, if they, if it smelled sweet to them, you're more compatible, right? So cool. That's amazing. They should make a Netflix dating show based on this. You should pitch this to Netflix. That's what you should do.

1:26:57 That would be your next big after after the you know, you did the book, you're doing all this talking. You do it. You're doing the scores, you're doing the research. I think that a Netflix show based on the neurochemistry of love and mixing with mixed above with love is blind. Would be. There you go. There you go. There you go. Wow. OK, If we find that in Netflix in a couple of years, then we know where they came up with that idea. I'll give you credit. Doctor, Doctor Larry Sherman, this is so much fun. Thank you so much for such an awesome and informative and entertaining conversation. And I hope to stay in touch and I hope to be able to do this again down the line. And I'm sure that a lot's going to change and there's going to be a lot of exciting things to talk about, so. Got you.

1:27:37 That was really fun. I really enjoyed it. Thanks. So. Much. Yeah, of course, of course. Take care. Have a great day. Thanks for the time you too.